Winter 2010 FDA Updates

March 3, 2011

Contemporary Oncology

Contemporary Oncology®, Winter 2010, Volume 2, Issue 4

FDA updates from Winter 2010

Voting 10-0, an Oncologic Drugs Advisory Committee recommended that the FDA approve AstraZeneca’s novel drug Zactima (vandetanib) for patients with medullary thyroid cancer, which is a rare form of the disease. Noting concerns about the drug’s potential to cause cerebrovascular events, including stroke, and prolonged QT intervals, the panel recommended restricting use of the drug to patients with symptomatic disease. Panel chair Wyndham Wilson, MD, chief of Lymphoma Therapeutics with the National Cancer Institute, said despite concerns about Zactima’s toxicity profile, “I think we all agree it’s a very effective new agent and should be made available.
Studies have touted the benefit of using 5-alpha reductase inhibitors, such as Avodart (dutasteride) and Proscar (finasteride), to reduce the risk of prostate cancer. These drugs are presently approved to treat benign prostatic hypertrophy. One trial found 4 years of chemoprevention with GlaxoSmithKline’s Avodart reduced prostate cancer risk by 23%. In advance of an upcoming advisory panel meeting, the FDA has posted briefing documents on its Website noting that dutasteride raised the incidence of high-risk prostate cancer. Merck, which manufactures Proscar, is asking to change its label to reflect study findings that show it reduced the rate of low-risk prostate cancer but is not seeking a new indication for the drug.
Spectrum Pharmaceuticals has received notice from the FDA that the agency will make a decision on whether to approve Fusilev (levoleucovorin) for colorectal cancer no later than April 29, 2011. The injectable drug is already available to treat osteosarcoma and to mitigate toxicity from methotrexate. Approximately 1 year ago, the FDA rejected Spectrum’s request to expand indications for Fusilev to include colorectal cancer, citing a lack of efficacy. The manufacturer compiled additional data supporting the new indication and submitted these to the FDA on October 29.
Approval of generic drug manufacturer Hospira’s formulation of docetaxel (marketed by sanofi-aventis as Taxotere) has been delayed pending approval of changes to the label and package insert requested by the FDA. The changes relate to the generic drug’s distribution in two 10-mg/mL vials, rather than the single 20-mg/mL vial that sanofi-aventis is now using. Hospira said that because the FDA’s concern is not with the drug itself, it anticipates that the generic version of docetaxel will receive final approval by the end of 2010.
The FDA has approved a proposed protocol for conducting a phase III clinical trial that will evaluate the safety and efficacy of QuadraSphere Microspheres in patients with localized, unresectable hepatocellular carcinoma. Merit Medical Systems, which manufactures the drug-eluting microspheres, says the study will enroll 500 patients and involve interventional radiologists from the United States, South America, and Europe. QuadraSphere Microspheres release doxorubicin and are currently approved for peripheral arteriovenous malformations and to embolize hypervascular tumors. The trial is being referred to as the HiQuality (HepaSphere/QuadraSphere in Liver Cancer Treatment) study.
Another new generic anticancer drug is about to enter the market, with the FDA’s approval of APP Pharmaceuticals’ formulation of topotecan. The injectable drug was first approved under the brand name Hycamtin, which is manufactured by GlaxoSmithKline. Topotecan is approved as a second-line treatment for small cell lung cancer and as part of a cisplatin-based regimen for advanced cervical cancer in certain circumstances: stage IV-B disease and recurrent or persistent disease that cannot be cured with surgery or radiotherapy. The company said in a press release that it plans to launch the drug immediately.
The Vaccines and Related Biological Products Advisory Committee recommended in November 2010 that the FDA grant approval to Merck to market its human papillomavirus vaccine Gardasil as prevention for anal cancer in males and females aged 9 to 26 years. In a press release, Ambrose Cheung, MD, a member of the committee and a professor of microbiology at Dartmouth Medical School, said, “I believe the rationale for [approving] the vaccine is there.” He described the data as “strong” and “very robust.” Merck is still waiting for an FDA response on whether it will approve expanding Gardasil’s existing indications for cervical, vulvar, and vaginal cancer and genital warts to include women aged 27 to 45 years.